Respiratory syncytial virus infection triggers HMGB1 release from lung epithelial cells to promote inflammatory cytokine production (CAM1P.152)

Abstract

Abstract Respiratory syncytial virus (RSV) is an important cause of lower respiratory tract infections in infants and young children. Oxidative stress is shown to play an important role in the pathogenesis of lung inflammation. We have shown that RSV induces oxidative stress by rapid generation of reactive oxygen species and downregulation of antioxidant enzyme expression resulting in lung inflammation. High mobility group box 1 protein (HMGB1) is a redox-sensitive multifunction protein that serves as both a chromatin protein and an extracellular signaling molecule. Although HMGB1 has been implicated in inflammatory diseases, there has been no report on its role in RSV related lung disease. The goal of this study is to dissect the mechanisms that induce the release of HMGB1 and associated cellular signaling in response to RSV infection. Human lung epithelial cells were infected with RSV and harvested over time to analyze HMGB1 expression by Western blot, immunohistochemistry and qRT-PCR. Our studies show for the first time that RSV infection induces the translocation of HMGB1 from cell nuclei to the cytoplasm and its subsequent release to the extracellular space demonstrating a novel mechanism of HMGB1 in the activation of cells to promote inflammatory cytokine release. Understanding of HMGB1 role in the setting of viral-induced oxidative stress may lead to the development of novel strategies to treat respiratory viral infections in pediatric and elderly population.